# Neurogranin regulation of nitric oxide signaling in cardiovascular disease

> **NIH NIH P20** · LOUISIANA STATE UNIV HSC SHREVEPORT · 2021 · $216,090

## Abstract

PROJECT ABSTRACT 
Schizophrenia patients have a greater rate of premature death from cardiovascular disease compared with the 
general population. Although the higher incidence of cardiovascular disease in schizophrenia patients is due to 
increased cardiovascular disease risk factors, new evidence suggests genetic susceptibility in this patient 
group may account for the greater risk of cardiovascular disease. Therefore, it is pertinent to identify 
mechanistic relationships that could act as a pathophysiological link between schizophrenia and cardiovascular 
disease. 
 Human clinical studies highlighted the link between a genetic variant of Neurogranin (Ng, 7.6 kDa), a 
calmodulin (CaM)-binding protein, thought to be exclusively expressed in the brain, and a risk of developing 
schizophrenia. Interestingly, we recently discovered that deletion of Ng in mice also resulted in significant 
cardiac dysfunction; it was associated with decreased ejection fraction and fractional shortening as well as 
perivascular fibrosis. Ng –/– mice also show decreased plasma nitric oxide (NO) levels, indicative of endothelial 
cell dysfunction, similar to the endothelial NO synthase (eNOS) dysfunction observed in schizophrenic 
patients. Our preliminary studies also demonstrated that Ng is highly expressed in the endothelium and 
significantly up-regulated in response to laminar flow, a known inducer of NO production. Thus, we 
hypothesize that Ng mediates Ca2+-dependent eNOS activity in the endothelium and that defects in Ng 
signaling increases vascular resistance resulting in cardiac fibrosis, hypertrophy, and eventually cardiac failure. 
 To test this hypothesis, AIM1 will determine the mechanistic role of Ng in eNOS signaling using in vitro 
approaches. We will test whether altered Ng expression using knockout (Ng siRNA and Ng CRISPR/Cas9 
knockout) and overexpression (Lentivirus-oNg and Lentivirus-dnNg) affect eNOS expression and the sensitivity 
of eNOS to inflammation. AIM2 will also determine the effect of Ng deletion on cardiovascular function in mice. 
We will conduct flow-mediated vasodilation and angiotensin II infusion to test the susceptibility of Ng-mediated 
vascular resistance and cardiac failure. The results of these aims will discover a novel Ng-eNOS mechanism in 
the endothelium that contributes to cardiac dysfunction. Moreover, these results will contribute to our goal of 
establishing clinical interventions between cardiovascular disease and schizophrenia and to positively impact 
treatment strategies for cardiovascular disease.

## Key facts

- **NIH application ID:** 10086882
- **Project number:** 5P20GM121307-04
- **Recipient organization:** LOUISIANA STATE UNIV HSC SHREVEPORT
- **Principal Investigator:** Hyung W Nam
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $216,090
- **Award type:** 5
- **Project period:** 2018-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10086882

## Citation

> US National Institutes of Health, RePORTER application 10086882, Neurogranin regulation of nitric oxide signaling in cardiovascular disease (5P20GM121307-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10086882. Licensed CC0.

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